Flow cytometers are use in research and clinical applications to analyze the characteristics of particles or cells. Typically, in these systems, a particle stream is injected into the center of a laminar sheath flow stream. The combined stream is passed through an interrogation region, where cells of interest are identified and/or characterized. With the addition of a sorting functionality, a flow cytometer can further be used to isolate particle(s) of interest from a sample. In droplet sorters, the stream may subsequently be divided into droplets, with droplets containing the cells of interest be sorted into separate collection chambers.
In conventional droplet sorters, a suspension including a sheath fluid and a sample containing particles passes through a nozzle and is formed into a focused fluid stream for particle detection and analysis. The fluid stream is oscillated with an oscillator to generate droplets. In order to sort particles within the fluid stream, the fluid stream may be charged just before a droplet containing a particle of interest separates from the fluid stream at a breakoff point. The droplet retains the charge and as it passes through an electromagnetic field downstream of the breakoff point it is directed to the desired location. A precise coordination between the particle detection and the droplet charging at the breakoff point is required. This drop delay parameter is one of the most important determinations required for performing accurate sort actions.
The stability of the flow of the fluid stream is especially important for sorting applications, because perturbations in the fluid flowing through the instrument may adversely impact the stability of the droplet break off point and thus the accuracy of the drop delay parameter. Accordingly, a sheath flow delivery system should provide sufficient flow capacity with a substantially invariant flow rate and pressure. Further, sheath flow delivery systems should provide stable sheath flow in the presence of variations in the operating environment (e.g., temperature, etc.), variations in the equipment operation (e.g., run-in, voltages, etc.), and variations in the fluid flowing through the system (e.g., pressures, viscosity, etc.). Additionally, a sheath flow delivery system should provide a sheath flow free of bubbles and should maintain the sterility of the sheath flow.
U.S. Pat. No. 8,597,573 to Gilligan (issued Dec. 3, 2013), which discloses a continuously regulated precision pressure fluid delivery system, is hereby incorporated by reference in its entirety herein. Gilligan discloses a fluid flow characteristic regulator which provides a variable volume flow path in which a fluid flow can be continuously adjusted by a control fluid to regulate at least one fluid flow characteristic of the fluid flow within the variable volume flow path.